Quantifying effectiveness and best practices for bumblebee identification from photographs.

Understanding pollinator networks requires species level data on pollinators. New photographic approaches to identification provide avenues to data collection that reduce impacts on declining bumblebee species, but limited research has addressed their accuracy. Using blind identification of 1418 photographed bees, of which 561 had paired specimens, we assessed identification and agreement across 20 bumblebee species netted in Montana, North Dakota, and South Dakota by people with minimal training. An expert identified 92.4% of bees from photographs, whereas 98.2% of bees were identified from specimens. Photograph identifiability decreased for bees that were wet or matted; bees without clear pictures of the abdomen, side of thorax, or top of thorax; bees photographed with a tablet, and for species with more color morphs. Across paired specimens, the identification matched for 95.1% of bees. When combined with a second opinion of specimens without matching identifications, data suggested a similar misidentification rate (2.7% for photographs and 2.5% specimens). We suggest approaches to maximize accuracy, including development of rulesets for collection of a subset of specimens based on difficulty of identification and to address cryptic variation, and focused training on identification that highlights detection of species of concern and species frequently confused in a study area.

Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study.

PURPOSE: In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. METHODS: Patients with clinical stage II-III HER2+ BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. RESULTS: In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). CONCLUSION: pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT02789657.

Evidence-based pain medicine for primary care physicians.

The last several decades have seen a marked increase in both the recognition and treatment of chronic pain. Unfortunately, patients frequently misunderstand both the nature of pain and the best practices for its treatment. Because primary care physicians treat the majority of chronic pain, they are ideally situated to provide evidence-based pain care. The majority of the medical evidence supports a biopsychosocial model of pain that integrates physical, emotional, social, and cultural variables. The goal of this primer is to assist primary care physicians in their understanding of pain, evaluation of the chronic pain patient, and ability to direct evidence-based care. This article will discuss the role of physical rehabilitation, pain psychology, pharmacotherapy, and procedural interventions in the treatment of chronic pain. Given the current epidemic of drug-related deaths, particular emphasis is placed on the alternatives to opioid therapy. Unfortunately, death is not the only significant complication from opioid therapy, and this article discusses many of the most common side effects. This article provides general guidelines on the most appropriate utilization of opioids with emphasis on the recent Centers for Disease Control and Prevention guidelines, risk stratification, and patient monitoring. Finally, the article concludes with the critical role that a pain medicine specialist can play in the management of patients with chronic pain.

A genomic case study of mixed fibrolamellar hepatocellular carcinoma.

BACKGROUND: Mixed fibrolamellar hepatocellular carcinoma (mFL-HCC) is a rare liver tumor defined by the presence of both pure FL-HCC and conventional HCC components, represents up to 25% of cases of FL-HCC, and has been associated with worse prognosis. Recent genomic characterization of pure FL-HCC identified a highly recurrent transcript fusion (DNAJB1:PRKACA) not found in conventional HCC. PATIENTS AND METHODS: We performed exome and transcriptome sequencing of a case of mFL-HCC. A novel BAC-capture approach was developed to identify a 400 kb deletion as the underlying genomic mechanism for a DNAJB1:PRKACA fusion in this case. A sensitive Nanostring Elements assay was used to screen for this transcript fusion in a second case of mFL-HCC, 112 additional HCC samples and 44 adjacent non-tumor liver samples. RESULTS: We report the first comprehensive genomic analysis of a case of mFL-HCC. No common HCC-associated mutations were identified. The very low mutation rate of this case, large number of mostly single-copy, long-range copy number variants, and high expression of ERBB2 were more consistent with previous reports of pure FL-HCC than conventional HCC. In particular, the DNAJB1:PRKACA fusion transcript specifically associated with pure FL-HCC was detected at very high expression levels. Subsequent analysis revealed the presence of this fusion in all primary and metastatic samples, including those with mixed or conventional HCC pathology. A second case of mFL-HCC confirmed our finding that the fusion was detectable in conventional components. An expanded screen identified a third case of fusion-positive HCC, which upon review, also had both conventional and fibrolamellar features. This screen confirmed the absence of the fusion in all conventional HCC and adjacent non-tumor liver samples. CONCLUSION: These results indicate that mFL-HCC is similar to pure FL-HCC at the genomic level and the DNAJB1:PRKACA fusion can be used as a diagnostic tool for both pure and mFL-HCC.

Fast shut-down protection system for radio frequency breakdown and multipactor testing.

Radio frequency (RF) breakdown such as multipactor or ionization breakdown is a device-limiting phenomenon for on-orbit spacecraft used for communication, navigation, or other RF payloads. Ground testing is therefore part of the qualification process for all high power components used in these space systems. This paper illustrates a shut-down protection system to be incorporated into multipactor/ionization breakdown ground testing for susceptible RF devices. This 8 channel system allows simultaneous use of different diagnostic classes and different noise floors. With initiation of a breakdown event, diagnostic signals increase above a user-specified level, which then opens an RF switch to eliminate RF power from the high power amplifier. Examples of this system in use are shown for a typical setup, illustrating the reproducibility of breakdown threshold voltages and the lack of multipactor conditioning. This system can also be utilized to prevent excessive damage to RF components in tests with sensitive or flight hardware.

Distribution of K and L cells in the feline intestinal tract.

Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)-1 and GLP-2 are hormones secreted from specialized K cells (GIP) and L cells (GLP-1, GLP-2) in the intestinal mucosa. These hormones play major roles in health and disease by modulating insulin secretion, satiety, and multiple intestinal functions. The aim of this study was to describe the distribution of K cells and L cells in the intestines of healthy cats. Samples of duodenum, mid-jejunum, ileum, cecum, and colon were collected from 5 cats that were euthanized for reasons unrelated to this study and had no gross or histologic evidence of gastrointestinal disease. Samples stained with rabbit-anti-porcine GIP, mouse-anti-(all mammals) GLP-1, or rabbit-anti-(all mammals) GLP-2 antibodies were used to determine the number of cells in 15 randomly selected 400× microscopic fields. In contrast to other mammals (eg, dogs) in which K cells are not present in the ileum and aborally, GIP-expressing cells are abundant throughout the intestines in cats (>6/high-power field in the ileum). Cells expressing GLP-1 or GLP-2 were most abundant in the ileum (>9/high-power field) as in other mammals, but, although GLP-1-expressing cells were abundant throughout the intestines, GLP-2-expressing cells were rarely found in the duodenum. In conclusion, the distribution of GIP-secreting K cells in cats is different from the distribution of K cells that is described in other mammals. The difference in distribution of GLP-2- and GLP-1-expressing cells suggests that more than 1 distinct population of L cells is present in cats.

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function.

Urine drug testing: current recommendations and best practices.

BACKGROUND: The precise role of urine drug testing (UDT) in the practice of pain medicine is currently being defined. Confusion exists as to best practices, and even to what constitutes standard of care. A member survey by our state pain society revealed variability in practice and a lack of consensus. OBJECTIVE: The authors sought to further clarify the importance of routine UDT as an important part of an overall treatment plan that includes chronic opioid prescribing. Further, we wish to clarify best practices based on consensus and data where available. METHODS: A 20-item membership survey was sent to Texas Pain Society members. A group of chronic pain experts from the Texas Pain Society undertook an effort to review the best practices in the literature. The rationale for current UDT practices is clarified, with risk management strategies outlined, and recommendations for UDT outlined in detail. A detailed insight into the limitations of point-of-care (enzyme-linked immunosorbent assay, test cups, test strips) versus the more sensitive and specific laboratory methods is provided. LIMITATIONS: Our membership survey was of a limited sample size in one geographic area in the United States and may not represent national patterns. Finally, there is limited data as to the efficacy of UDT practices in improving compliance and curtailing overall medication misuse. CONCLUSIONS: UDT must be done routinely as part of an overall best practice program in order to prescribe chronic opioid therapy. This program may include risk stratification; baseline and periodic UDT; behavioral monitoring; and prescription monitoring programs as the best available tools to monitor chronic opioid compliance.

The GLP-1 mimetic exenatide potentiates insulin secretion in healthy cats.

The glucagon-like peptide-1 mimetic exenatide has a glucose-dependent insulinotropic effect, and it is effective in controlling blood glucose (BG) with minimal side effects in people with type 2 diabetes. Exenatide also delays gastric emptying, increases satiety, and improves ß-cell function. We studied the effect of exenatide on insulin secretion during euglycemia and hyperglycemia in cats. Nine young, healthy, neutered, purpose-bred cats were used in a randomized, cross-over design. BG concentrations during an oral glucose tolerance test were determined in these cats previously. Two isoglycemic glucose clamps (mimicking the BG concentration during the oral glucose tolerance test) were performed in each cat on separate days, one without prior treatment (IGC) and the second with exenatide (1 µg/kg) injected subcutaneously 2 h before (ExIGC). BG, insulin, and exenatide concentrations were measured, and glucose infusion rates were recorded and compared in paired tests between the two experiments. After exenatide injection, insulin serum concentrations increased significantly (2.4-fold; range 1.0- to 9.2-fold; P = 0.004) within 15 min. This was followed by a mild decrease in BG concentration and a return of insulin concentration to baseline despite a continuous increase in serum exenatide concentrations. Insulin area under the curve (AUC) during ExIGC was significantly higher than insulin AUC during IGC (AUC ratio, 2.0 ± 0.4; P = 0.03). Total glucose infused was not significantly different between IGC and ExIGC. Exenatide was detectable in plasma at 15 min after injection. The mean exenatide concentration peaked at 45 min and then returned to baseline by 75 min. Exenatide was still detectable in the serum of three of five cats 8 h after injection. No adverse reactions to exenatide were observed. In conclusion, exenatide affects insulin secretion in cats in a glucose-dependent manner, similar to its effect in other species. Although this effect was not accompanied by a greater ability to dispose of an intravenous glucose infusion, other potentially beneficial effects of exenatide on pancreatic ß cells, mainly increasing their proliferation and survival, should be investigated in cats.

The incretin effect in cats: comparison between oral glucose, lipids, and amino acids.

Incretin hormones are secreted from the intestines in response to specific nutrients. They potentiate insulin secretion and have other beneficial effects in glucose homeostasis. We aimed to study the incretin effect in cats and to compare the effect of oral glucose, lipids, or amino acids on serum concentrations of insulin, total glucose-dependent insulinotropic peptide (GIP) and total glucagon-like peptide 1 (GLP-1). Ten healthy cats were used in a repeated measures design. Glucose, lipid, or amino acids were administered through nasoesophageal tubes on separate days. Blood glucose (BG) concentrations were matched between experiments by measuring BG every 5 min and infusing glucose intravenously at a changing rate. Intravenous glucose infusion with no prior treatment served as control. The incretin effect was estimated as the difference in insulin area under the curve (AUC) after oral compared with intravenous glucose. Temporal changes and total amount of hormone secretions were compared between treatment groups with the use of mixed models. Total glucose infused (TGI) at a mean dose of 0.49 g/kg resulted in slightly higher BG compared with 1 g/kg oral glucose (P = 0.038), but insulin concentrations were not significantly different (P = 0.367). BG and the TGI were not significantly different after the 3 oral challenges. Total GIP AUC was larger after lipids compared with amino acids (P = 0.0012) but GIP concentrations did not increase after oral glucose. Insulin and GIP concentrations were positively correlated after lipid (P < 0.001) and amino acids (P < 0.001) stimulations, respectively, but not after oral glucose stimulation. Total GLP-1 AUC was similar after all three oral stimulations. Insulin and GLP-1 concentrations were positively correlated after glucose (P = 0.001), amino acids (P < 0.001), or lipids (P = 0.001) stimulations. Our data indirectly support an insulinotropic effect of GIP and GLP-1. Potentiation of insulin secretion after oral glucose is minimal in cats and is mediated by GLP-1 but not GIP.

Dietary macronutrients and feeding frequency affect fasting and postprandial concentrations of hormones involved in appetite regulation in adult dogs.

Identifying dietary effects on appetite-regulating hormones will enhance our understanding of appetite control. Before complex diets are tested, effects of specific macronutrients or feeding frequency should be identified. The objectives of this nutrition study were to identify differences in endocrine response with feeding frequency (Exp. 1) and after a single dose of a sole macronutrient (Exp. 2). A control diet supplying similar energy content from carbohydrate, protein, and fat was fed to maintain ideal BW. In Exp. 1, 8 healthy adult (1.9 ± 0.1 yr old) female hound cross dogs with an average BW of 22 kg (4.8 ± 0.8 BCS based on a 9-point scale) were randomly allotted to 1 of 2 treatments (fed once or twice daily) in a crossover design. After a 14-d adaptation period, a blood sample was taken (10 mL) before feeding, and samples were collected every 2 h postprandially for 24 h. In Exp. 2, dogs were randomly allotted to 1 of 4 treatments in a 4 × 4 Latin square design. After a 6-d adaptation period, the normal meal on d 7 was replaced with a bolus of maltodextrin (50 g in water; CARB), canned chicken (50 g; PROT), lard (25 g; fat), or water (200 mL). A blood sample (10 mL) was taken at 0, 30, 60, 90, 120, 150, 180, 240, 300, and 360 min postprandial. Total ghrelin, active glucagon-like peptide-1 (GLP-1), insulin, and glucose concentrations were measured. Data were analyzed to compare changes from baseline and area under the curve (AUC) among treatments. In Exp. 1, all hormones were quite variable throughout the day, with a few insulin and GLP-1 differences because of feeding frequency. In Exp. 2, CARB produced a marked peak in glucose and insulin concentrations compared with PROT, fat, or water, resulting in increased glucose (P < 0.001) and insulin (P = 0.07) incremental AUC values. On the other hand, the fat treatment led to increased GLP-1 concentrations over time. Ghrelin AUC was not different among treatments. The circulating hormone data were highly variable and indicate that diet plays a role in insulin and GLP-1 secretion, but more research is required to elucidate these effects.

Effectiveness of a group opt-in session on uptake and graduation rates for pulmonary rehabilitation.

Pulmonary rehabilitation (PR) is an effective intervention in the treatment of patients with chronic obstructive pulmonary disease (COPD). Unfortunately some patients offered this treatment either fail to take up the offer or fail to complete the course. Studies have indicated a number of factors influencing uptake and completion rates. We describe the introduction of an intervention, the group opt-in session (GOIS), prior to individualised baseline assessment and entry to the PR course, with the intention being to improve uptake and completion rates. A 1.5-hour-long GOIS was offered as the first face-to-face contact to all patients referred for PR. Drop-out rates at all stages of the pathway from referral to graduation were collected on 200 patients prior to the introduction of the GOIS (non-GOIS group) and compared to the first 400 patients following introduction (the GOIS group). Possible independent predictors of course uptake and completion were examined in the GOIS group. The proportion of referred patients taking up the offer of individualised baseline assessment or a GOIS was similar (75% vs. 72.2%, p value not significant [ns]). However, since in the GOIS group the opt-in session preceded the individualised baseline assessment and some patients opted-out, a smaller proportion of referred patients underwent this assessment than in the non-GOIS group (58.7% vs. 75%, p < 0.001). In addition, dropouts following individualised baseline assessments were also reduced (7% vs. 22%, p < 0.001). Both of these factors reduced 'wasted' assessments. Similar proportions of patients referred began the PR course in both groups (53% vs. 51.7%, ns), but a higher proportion of patients graduated in the GOIS group (87.9% vs. 76.4%, p < 0.05). Drop-out rates due to illness were similar in both groups (8.5% pre vs. 6.8% post, ns). However, drop-out rates not due to illness were much higher in the non-GOIS group (15.1% vs. 5.3%, p < 0.001). In the GOIS group, patients who did not attend the GOIS were, on average, younger (64.6 years vs. 69.7 years, p < 0.001) and had a higher mean percent predicted Forced Expiratory Volume (50.6% vs. 43.8%, p < 0.05) than those that did attend. A greater proportion of patients who opted in to the GOIS and attended the PR course lived less than 25 minutes from the PR centre than either those who did not attend the GOIS or who attended and then opted out (77.4% vs. 63%, p<0.005). The GOIS improved the graduation rates at The North Bristol Lung Centre PR Course and reduced wasted assessments. There was no effect on initial uptake. Analysis of the behaviour of patients invited to a GOIS suggested that age, lung function and travel distance were important factors influencing patient choice.

Nongenetic factors influence severity of episodic ataxia type 1 in monozygotic twins.

OBJECTIVE: Episodic ataxia type 1 (EA1) is a monogenic channelopathy caused by mutations of the potassium channel gene KCNA1. Affected individuals carrying the same mutation can exhibit considerable variability in the severity of ataxia, neuromyotonia, and other associated features. We investigated the phenotypic heterogeneity of EA1 in 2 sets of identical twins to determine the contribution of environmental factors to disease severity. One of the mutations was also found in a distantly related family, providing evidence of the influence of genetic background on the EA1 phenotype. METHODS: We evaluated 3 families with an EA1 phenotype, 2 of which included monozygotic twins. We sequenced the KCNA1 gene and studied the biophysical consequences of the mutations in HEK cells. RESULTS: We identified a new KCNA1 mutation in each pair of twins. Both pairs reported striking differences in the clinical severity of symptoms. The F414S mutation identified in one set of twins also occurred in a distantly related family in which seizures complicated the EA1 phenotype. The other twins had an R307C mutation, the first EA1 mutation to affect an arginine residue in the voltage-sensor domain. Both mutants when expressed exerted a dominant-negative effect on wild-type channels. CONCLUSION: These results broaden the range of KCNA1 mutations and reveal an unexpectedly large contribution of nongenetic factors to phenotypic variability in EA1. The occurrence of epilepsy in 1 of 2 families with the F414S mutation suggests an interplay of KCNA1 with other genetic factors.

Pharmacodynamics of insulin detemir and insulin glargine assessed by an isoglycemic clamp method in healthy cats.

BACKGROUND: Insulin detemir and insulin glargine are synthetic long-acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time-action profile, while insulin detemir has significantly less within-subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. OBJECTIVES: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. ANIMALS: Ten young, healthy, neutered, purpose-bred cats. METHODS: Randomized, cross-over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection. RESULTS: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8+/-0.8 and 1.3+/-0.5 hours for insulin detemir and insulin glargine, respectively, P=.03). End of action of insulin detemir was reached at 13.5+/-3.5 hours and for insulin glargine at 11.3+/-4.5 hours (P=.18). Time-to-peak action of insulin detemir was reached at 6.9+/-3.1 hours and for insulin glargine at 5.3+/-3.8 hours (P=.7). The time-action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others. CONCLUSION AND CLINICAL IMPORTANCE: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once-a-day drugs. Peak effects of both insulin analogs are pronounced in some cats.

Cloning and sequencing of the calcium-sensing receptor from the feline parathyroid gland.

Messenger RNA of the calcium-sensing receptor from feline parathyroid gland (fCaSR) was reversed transcribed to cDNA, amplified by polymerase chain reaction (PCR) and cloned into E. coli. Sequences obtained from cloned E. coli were used for genetic characterization of the fCaSR mRNA and for exonic PCR primer design. Multiple fCaSR exons sequence alignments obtained from PCR amplification of genomic DNA of 5 healthy domestic shorthair cats indicated the presence of 3 synonymous missense single-nucleotide polymorphisms (SNP) and 1 nonsynonymous missense SNP, which changed an amino acid from arginine to proline. The fCaSR has 96%, 96%, and 94% homology to the canine, human, and bovine amino acid sequences, respectively.

Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing.

BACKGROUND: Episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are autosomal dominant disorders characterised by paroxysmal ataxia and migraine, respectively. Point mutations in CACNA1A, which encodes the neuronal P/Q-type calcium channel, have been detected in many cases of EA2 and FHM1. The genetic basis of typical cases without CACNA1A point mutations is not fully known. Standard DNA sequencing methods may miss large scale genetic rearrangements such as deletions and duplications. The authors investigated whether large scale genetic rearrangements in CACNA1A can cause EA2 and FHM1. METHODS: The authors used multiplex ligation dependent probe amplification (MLPA) to screen for intragenic CACNA1A rearrangements. RESULTS: The authors identified five previously unreported large scale deletions in CACNA1A in seven families with episodic ataxia and in one case with hemiplegic migraine. One of the deletions (exon 6 of CACNA1A) segregated with episodic ataxia in a four generation family with eight affected individuals previously mapped to 19p13. In addition, the authors identified the first pathogenic duplication in CACNA1A in an index case with isolated episodic diplopia without ataxia and in a first degree relative with episodic ataxia. CONCLUSIONS: Large scale deletions and duplications can cause CACNA1A associated channelopathies. Direct DNA sequencing alone is not sufficient as a diagnostic screening test.

Impact of ovariohysterectomy and food intake on body composition, physical activity, and adipose gene expression in cats.

The mechanisms contributing to BW gain following ovariohysterectomy in domestic cats are poorly understood. Moreover, the effects of food restriction to maintain BW following spaying have been poorly studied. Thus, our primary objective was to determine the effects of spaying and food restriction to maintain BW on adipose and skeletal muscle mRNA abundance and activity levels in cats. After a 4-wk baseline period (wk 0), 8 adult (approximately 1.5 yr old) domestic shorthair cats were spayed and fed to maintain BW for 12 wk. After 12 wk, cats were fed ad libitum for an additional 12 wk. Body composition was determined, activity levels were measured, and adipose and muscle biopsies were collected at wk 0, 12, and 24. Fasting blood samples were collected at wk 0, 6, 12, 18, and 24. To maintain BW post-spay, food intake was decreased (P < 0.05) by 30%. During this phase, mRNA abundance of adipose tissue lipoprotein lipase and leptin was decreased (P < 0.05), representing only 52 and 23% of baseline expression, respectively. Interleukin-6 mRNA, however, was increased (P < 0.05) 2-fold. Physical activity was decreased (P < 0.05) by wk 12, most dramatically during the dark period (approximately 20% of baseline activity). During ad libitum feeding (wk 12 to 24), food intake, BW, body fat percentage, and total fat mass were greatly increased (P < 0.05). Compared with wk 0, circulating leptin concentrations tended to increase (P < 0.10) by wk 18 and 24 (4.45 vs. 10.02 and 9.14 ng/mL, respectively), whereas glucose (91 vs. 162 mg/dL) and triacylglyceride (30 vs. 48 mg/dL) concentrations were increased (P < 0.05) by wk 24. Adipose tissue lipoprotein lipase, hormone sensitive lipase, and adiponectin mRNA were decreased (P < 0.05) at wk 24. Adipose interleukin-6 mRNA was increased (P < 0.05) at 24 wk. Physical activity was further decreased (P < 0.05) by wk 24, during the light (60% of baseline) and dark (33% of baseline) periods. In summary, spaying and food restriction affect physical activity levels and several genes associated with lipid metabolism (decreased lipoprotein lipase), food intake (decreased leptin expression), and insulin insensitivity (increased interleukin-6). By identifying these changes, targets for nutritional intervention or lifestyle management have been identified that may curb the risk of obesity and related disorders in spayed cats.

Ovariohysterectomy alters body composition and adipose and skeletal muscle gene expression in cats fed a high-protein or moderate-protein diet.

The objective of this study was to measure changes in body composition, physical activity and adipose and skeletal muscle gene expression of cats fed a high-protein (HP) diet or moderate-protein (MP) diet, following ovariohysterectomy. Eight cats were randomized onto HP or MP diets and were fed those diets for several months prior to baseline. All cats underwent an ovariohysterectomy at baseline (week 0) and were allowed ad libitum access to dietary treatments for 24 weeks. Food intake was measured daily, and BW and body condition score were measured weekly. Blood, adipose and skeletal muscle tissue samples were collected, physical activity was measured, and body composition was determined using DEXA (dual-energy X-ray absorptiometry) at weeks 0, 12 and 24. Caloric intake increased soon after ovariohysterectomy, resulting in increased (P < 0.05) BW at weeks 12 and 24 compared to week 0. Body condition score and body fat percentage increased (P < 0.05) over time. Blood glucose increased (P < 0.05) linearly over time. Non-esterified fatty acids were decreased (P < 0.05) at weeks 12 and 24 compared to week 0. Blood leptin increased (P < 0.05) over time. Total physical activity decreased (P < 0.05) from week 0 to weeks 12 and 24 in all cats. Adipose tissue mRNA abundance of adiponectin, hormone sensitive lipase, toll-like receptor-4, uncoupling protein-2 (UCP2) and vascular endothelial growth factor decreased (P < 0.05) linearly over time, regardless of diet. Skeletal muscle mRNA abundance for glucose transporter-1, hormone sensitive lipase and UCP2 were decreased (P < 0.05), regardless of dietary treatment. Our research noted metabolic changes following ovariohysterectomy that are in agreement with gene expression changes pertaining to lipid metabolism. Feeding cats ad libitum after ovariohysterectomy is inadvisable.